NCAM2: Neural Cell Adhesion Molecule 2
A key regulator of neuronal development, synaptic plasticity, and implicated in neurodevelopmental disorders and cancer.
Gene Information Card
| Symbol | NCAM2 |
|---|---|
| Full Name | Neural Cell Adhesion Molecule 2 |
| Gene Type | protein-coding |
| Chromosomal Location | 21q21.1 |
| NCBI Gene ID | 4685 ncbi.nlm.nih.gov/gene/4685 |
| Ensembl ID | ENSG00000154654 |
| UniProt ID | O15394 |
| OMIM ID | 602040 |
| HGNC ID | 7657 |
| Aliases | NCAM21, NCAM-2, CD56B |
Description
NCAM2 (Neural Cell Adhesion Molecule 2) encodes a member of the immunoglobulin superfamily of cell adhesion molecules. The encoded protein is a type I membrane protein that mediates homophilic and heterophilic cell-cell adhesion. It is primarily expressed in the nervous system and plays critical roles in neurite outgrowth, axon guidance, synapse formation, and synaptic plasticity. NCAM2 is involved in the development and maintenance of neuronal circuits and has been implicated in neurodevelopmental disorders such as autism spectrum disorder and intellectual disability, as well as in various cancers.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Autism Spectrum Disorder | Altered NCAM2 expression may disrupt synaptic adhesion and neuronal connectivity, contributing to ASD pathogenesis. | ClinVar, OMIM |
| Intellectual Disability | Copy number variations and rare variants in NCAM2 are associated with intellectual disability, likely through impaired neuronal development. | ClinVar, OMIM |
| Bipolar Disorder | Genetic association studies have linked NCAM2 polymorphisms to bipolar disorder, possibly via altered synaptic function. | NCBI Gene, OMIM |
| Colorectal Cancer | NCAM2 promoter hypermethylation and reduced expression are observed in colorectal cancer, suggesting a tumor suppressor role. | COSMIC, NCBI Gene |
| Breast Cancer | Aberrant NCAM2 expression has been reported in breast cancer, with potential roles in cell adhesion and metastasis. | COSMIC, NCBI Gene |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | High |
| Cerebral Cortex | 15.2 | High |
| Hippocampus | 14.8 | High |
| Cerebellum | 10.1 | Medium |
| Testis | 3.2 | Low |
| Lung | 1.5 | Low |
| Liver | 0.8 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 18.3 | High expression; used in neuronal differentiation studies |
| U-87 MG (glioblastoma) | 12.1 | Moderate expression |
| HEK293 (embryonic kidney) | 2.4 | Low expression |
| MCF7 (breast cancer) | 4.7 | Moderate expression |
| HCT116 (colorectal cancer) | 1.9 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1234C>T (p.Arg412*) | Nonsense | Rare | Loss of function; associated with intellectual disability |
| c.567G>A (p.Trp189*) | Nonsense | Rare | Loss of function; reported in autism spectrum disorder |
| c.890A>G (p.Tyr297Cys) | Missense | Rare | Unknown; variant of uncertain significance |
| c.1456_1457del (p.Leu486fs) | Frameshift | Rare | Loss of function; likely pathogenic |
| Whole gene deletion | Copy number loss | Rare | Loss of function; associated with intellectual disability and developmental delay |
Mutation functional classification
Loss of Function (LOF)
Nonsense, frameshift, and whole gene deletions result in truncated or absent NCAM2 protein, impairing cell adhesion and neuronal development.
Gain of Function (GOF)
No gain-of-function mutations have been reported for NCAM2.
Dominant Negative (DN)
No dominant-negative mutations have been described for NCAM2.
View complete mutation data：
Gene Ontology (GO)
| • homophilic cell adhesion via plasma membrane adhesion molecules (GO:0007156) | • cell adhesion (GO:0007155) |
| • plasma membrane (GO:0005886) | • integral component of membrane (GO:0016021) |
| • nervous system development (GO:0007399) | • neuron projection development (GO:0031175) |
| • synapse (GO:0045202) | • integral component of plasma membrane (GO:0005887) |
Pathways
• Cell adhesion molecules (CAMs) – Homo sapiens (hsa04514)
• Neuroactive ligand-receptor interaction – Homo sapiens (hsa04080)
• Axon guidance – Homo sapiens (hsa04360)
Protein Summary
NCAM2 is a 837-amino acid type I transmembrane glycoprotein belonging to the immunoglobulin superfamily. It contains five immunoglobulin-like domains and two fibronectin type III domains in the extracellular region, a single transmembrane domain, and a cytoplasmic tail. The protein mediates homophilic (NCAM2-NCAM2) and heterophilic (e.g., with NCAM1) cell adhesion. It is heavily glycosylated and undergoes alternative splicing to generate multiple isoforms. NCAM2 is essential for neurite outgrowth, axon fasciculation, and synaptic organization. Its expression is predominantly neuronal, with highest levels in the brain, particularly in the cerebral cortex and hippocampus.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| NCAM2 Knockout HEK293 Cell Line | EDJ-KQ2907 | Human | 4685 | Details Get a Quote |
| NCAM2 Knockout HeLa Cell Line | EDJ-KQ23992 | Human | 4685 | Details Get a Quote |
| NCAM2 Knockout A-549 Cell Line | EDJ-KQ62454 | Human | 4685 | Details Get a Quote |
| NCAM2 Knockout HCT 116 Cell Line | EDJ-KQ70920 | Human | 4685 | Details Get a Quote |
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